Ovarian embryonal rhabdomyosarcoma is a rare manifestation of the DICER1 syndrome

Leanne de Kock; Harriet Druker; Evan Weber; Nancy Hamel; Jeffrey Traubici; David Malkin; Jocelyne Arseneau; Colin J R Stewart; Dorothée Bouron-Dal Soglio; John R Priest; William D Foulkes

doi:10.1016/j.humpath.2015.02.008

Ovarian embryonal rhabdomyosarcoma is a rare manifestation of the DICER1 syndrome

Hum Pathol. 2015 Jun;46(6):917-22. doi: 10.1016/j.humpath.2015.02.008. Epub 2015 Mar 5.

Authors

Affiliations

¹ Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3A 0G4; Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2.
² Division of Hematology/Oncology, The Hospital for Sick Children, Department of Molecular and Medical Genetics, The University of Toronto, Toronto, Ontario, Canada M5G 1X8.
³ Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3H 2R9.
⁴ Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
⁵ Division of Hematology/Oncology, The Hospital for Sick Children, Departments of Pediatrics Medical Biophysics, The University of Toronto, Toronto, Ontario, Canada M5G 1X8.
⁶ Department of Pathology, McGill University, Montreal, Quebec, Canada H3A 2B4.
⁷ School for Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia WA 6008.
⁸ Department of Pathology, CHU-Sainte Justine and University of Montreal, Montréal, Quebec, Canada H3T 1C5.
⁹ Minneapolis, MN 55414.
¹⁰ Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3A 0G4; Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2; Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3H 2R9; Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada H2W 1S6. Electronic address: william.foulkes@mcgill.ca.

PMID: 25836323
DOI: 10.1016/j.humpath.2015.02.008

Abstract

Embryonal rhabdomyosarcoma (ERMS), a soft tissue sarcoma, is one of the most common pediatric cancers. Certain ERMSs are associated with the DICER1 syndrome, a tumor predisposition syndrome caused by germ-line DICER1 mutations. Characteristic somatic mutations have also been identified in DICER1-associated tumor types. These "hotspot" mutations affect the catalytic activity of the DICER1 ribonuclease IIIb domain. Primary ovarian ERMS (oERMS) is extremely rare. We present a case of a 6-year-old girl with an oERMS harboring 2 DICER1 mutations. The girl also exhibited other DICER1 phenotypes: cystic nephroma (CN) and multinodular goiter. Somatic investigations of the CN identified a hotspot DICER1 mutation different from that in the oERMS. Significantly, the CN presented at 12 years of age, which is much older than the previously reported age range of susceptibility. This report documents the occurrence of DICER1 mutations in a case of oERMS, expanding the spectrum of DICER1-associated tumors.

Keywords: DICER1; Embryonal rhabdomyosarcoma; Ovary; Pediatric tumors; miRNA.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Child
DEAD-box RNA Helicases / genetics*
DEAD-box RNA Helicases / metabolism
Female
Humans
MicroRNAs / genetics
Mutation / genetics*
Ovarian Neoplasms / diagnosis
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / pathology*
Phenotype
Rhabdomyosarcoma, Embryonal / diagnosis
Rhabdomyosarcoma, Embryonal / genetics*
Rhabdomyosarcoma, Embryonal / pathology*
Ribonuclease III / genetics*
Ribonuclease III / metabolism

Substances

MicroRNAs
DICER1 protein, human
Ribonuclease III
DEAD-box RNA Helicases

Grants and funding

FRN53888/Canadian Institutes of Health Research/Canada